Dentifrice compositions for treatment of dental biofilm

ABSTRACT

Dentifrice compositions comprising zinc lactate, glycine, and fluoride ion are provided for treating dental plaque biofilm.

FIELD OF THE INVENTION

The present invention relates to dentifrice compositions having improvedefficacy to help inhibit biofilm formation or help disrupt biofilm.

BACKGROUND OF THE INVENTION

Dental plaque (also known as dental biofilm) is a sticky, colorlessdeposit of bacteria that is constantly forming on the tooth surface.Dental plaque is generally made up of bacteria and extracellular polymersubstances (so called “EPS”). EPS are biopolymers of microbial origin inwhich biofilm microorganisms are embedded. J. Bacteriol. 2007,189(22):7945. Saliva, food and fluids combine to produce these depositsthat collect where the teeth and gums meet. Plaque buildup is theprimary factor in poor oral health that can lead to caries andperiodontal (gum) disease, including gingivitis. One way that dentifricecompositions help to prevent and control plaque is by leveraginganti-bacterial agents such as zinc ion source. However, the disadvantageor formulation challenge is the unintended reactivity of anti-bacterialagents with formulation ingredients and environment of dentifricematrix. This may include oxidative degradation, hydrolysis, adsorptionor precipitation of oxy-hydroxide species, any of which can impact thebio-availability of the anti-bacterial agent. Another problem offormulating a zinc containing dentifrice is astringency, anorganoleptically displeasing effect on the zinc ion. Therefore, there isa continuing need to provide a dentifrice formulation that help preventplaque formation on teeth, and at the same time having reducedastringency.

SUMMARY OF THE INVENTION

The present invention is based on the surprising discovery that thecombination of zinc lactate and glycine in a dentifrice compositionhelps the disruption and destabilization of the biofilm EPSarchitecture. It is further surprisingly found that the penetrationdepth and/or penetration rate of zinc ion into the biofilms isincreased, when used in combination with glycine. Further, the use ofthe glycine improves the sensorial experience reducing the associatedastringency and metallic taste of zinc that will ensure productcompliance and usage habit to deliver the oral health benefits.

An advantage of the present invention is the dentifrice composition ofthe present invention containing zinc lactate and glycine, intend todestabilize and disrupt the biofilm EPS architecture to aid the deliveryand penetration of actives to biofilms for optimizing efficacy.

Another advantage of the present invention is, as a result of thedestabilized dental biofilm (reduced thickness, biovolume and increasedporosity), it leads to improved delivery of the fluoride ion to thetooth surface to aid with the enamel remineralization cycle.

Yet another advantage of the present invention is that the dentifricecomposition can provide a reduced astringency, so as to provide theconsumer a better sensorial experience.

Still another advantage of the present invention is a phase stableformulation.

One aspect of the invention provides for a dentifrice compositioncomprising: a) from 0.2% to 2.0%, by weight of the composition, of azinc lactate; b) from 0.1% to 6.0%, by weight of the composition, of aglycine or salt thereof, or combination thereof; and c) from 0.05% to0.5%, by weight of the composition, of a fluoride ion.

Another aspect of the invention provides a method of treating dentalbiofilm comprising the step of brushing teeth with a composition of thepresent invention.

Yet another aspect of the invention provides a method reducing biofilmthickness and preventing or mitigating plaque formation on tooth enamelcomprising the step of brushing teeth with a dentifrice composition ofthe present invention.

An advantage of the present invention is the relatively costeffectiveness of the formulation by relatively high level of water andminimizing other ingredients (such as humectants).

These and other features, aspects, and advantages of the presentinvention will become evident to those skilled in the art from thedetailed description which follows.

BRIEF DESCRIPTION OF THE DRAWINGS

While the specification concludes with claims that particularly pointout and distinctly claim the invention, it is believed the presentinvention will be better understood from the following description ofthe accompanying figures.

FIG. 1 is a perspective view of an oral splint with Hydroxyapatite(“HA”) disks attached thereto.

FIG. 2 is a perspective view of the HA disk having grooves therein.

FIG. 3 is a schematic of a cross sectional view of the groove withbiofilm therein.

DETAILED DESCRIPTION OF THE INVENTION Definitions

As used herein, the articles including “a” and “an” when used in aclaim, are understood to mean one or more of what is claimed ordescribed.

The term “comprising” as used herein means that steps and ingredientsother than those specifically mentioned can be added. This termencompasses the terms “consisting of” and “consisting essentially of.”The compositions of the present invention can comprise, consist of, andconsist essentially of the essential elements and limitations of theinvention described herein, as well as any of the additional or optionalingredients, components, steps, or limitations described herein.

As used herein, the words “preferred”, “preferably” and variants referto embodiments of the invention that afford certain benefits, undercertain circumstances. However, other embodiments may also be preferred,under the same or other circumstances. Furthermore, the recitation ofone or more preferred embodiments does not imply that other embodimentsare not useful, and is not intended to exclude other embodiments fromthe scope of the invention.

The term “substantially free” as used herein refers to no intentionalamount of that material is added to the composition or an amount of amaterial that is less than 0.05%, 0.01%, or 0.001% of the composition.The term “essentially free” as used herein means that the indicatedmaterial is not deliberately added to the composition, or preferably notpresent at analytically detectable levels. It is meant to includecompositions whereby the indicated material is present only as animpurity of one of the other materials deliberately added. The term“free” as used herein refers to no reasonably detectable amount of thatmaterial is present in the composition.

The term “dentifrice” as used herein means paste, gel, powder, tablets,or liquid formulations, unless otherwise specified, that are used toclean the surfaces of the oral cavity. Preferably the dentifricecompositions of the present invention are single phase compositions. Oneexample of a dentifrice is toothpaste (for brushing teeth). The term“teeth” as used herein refers to natural teeth as well as artificialteeth or dental prosthesis.

All percentages, parts and ratios are based upon the total weight of thecompositions of the present invention, unless otherwise specified. Allsuch weights as they pertain to listed ingredients are based on theactive level and, therefore do not include solvents or by-products thatmay be included in commercially available materials, unless otherwisespecified.

All measurements referred to herein are made at 25° C. (i.e., roomtemperature) unless otherwise specified.

Dentifrice Compositions

It has been surprisingly discovered that the combination of zinc lactateand glycine in a dentifrice composition is particularly useful fortreatment of dental biofilm. In particular, the surprising discovery isthat the thickness of biofilm has been significantly reduced thus thepenetration of the zinc ion into the biofilms is markedly improved whencombined with glycine. Without wishing to be bound by theory, theneutral amino acid contains both carboxylic and amine groups. Zinclactate is used as a desired anti-bacteria agent in the dentifriceformulation because the zinc is already combined with a suitablechelating agent in the form of a salt. The chelation of the zinc throughlactate gives a controllable release of the Zn²⁺ species, which aredesired for the therapeutic effects. However, the associated Zn²⁺species impart a noticeable astringency of the sensorial experience.Surprisingly, the use of the glycine creates an ion exchange within thebiofilm to reduce the Ca/EPS ratio, resulting in a reduction in biofilmthickness. It has also been surprisingly found that the penetrationdepth and/or the penetration rate of zinc ions into the biofilms may beincreased, or markedly increased, when formulated with glycine. Inshort, the presence of glycine in combination with zinc lactate in adentifrice composition aids the composition's efficacy in mediating theharmful effects of the bacteria in the biofilms on the gums. Suchformulation also surprisingly reduces the sensorial astringency of thedentifrice.

In one aspect, the present invention is directed to a dentifricecomposition comprising: a) from 0.2% to 2.0%, by weight of thecomposition, of a zinc lactate; b) from 0.1% to 6.0%, by weight of thecomposition, of a glycine or salt thereof, or combination thereof; andc) from 0.05% to 0.5%, by weight of the composition, of a fluoride ion.

In some examples, the zinc lactate is present in a level of from 0.4% to1.8%, preferably from 0.5% to 1.5%, by weight of the composition. forexample, zinc lactate can be present in the composition in a level ofabout 0.6%, or about 0.7%, or about 0.8%, or about 0.9%, or about 1.0%,or about 1.1%, or about 1.2%, or about 1.35, or about 1.3%, by weight ofthe composition.

Alternatively, the dentifrice composition may comprise a source of zincions sufficient to provide from 0.05% to 0.5%, preferably from 0.1% to0.5%, or more preferably from 0.15% to 0.45% of soluble zinc ions byweight of the composition. For example, the dentifrice composition cancomprise about 1000 ppm, or about 1500 ppm, or about 2000 ppm, or about2500 ppm, or about 3000 ppm, or about 3500 ppm, or about 4000 ppm, byweight of the composition, of soluble zinc ion.

The dentifrice composition of the present invention may further compriseanother zinc ion source selected from zinc organic salts, preferablyselected from the group consisting of zinc citrate, zinc gluconate, andcombinations thereof.

In some alternative examples, the dentifrice composition may furthercomprise insoluble or sparingly soluble zinc compounds, such as zincoxide, zinc carbonate or zinc phosphate as the zinc ion source. But inother examples, the dentifrice composition does not comprise zinc oxideor other insoluble zinc salts such as zinc carbonate or zinc phosphate.In some alternative examples, the dentifrice composition may furthercomprise soluble zinc inorganic salts such as zinc chloride or zincsulfate. But in other examples, the dentifrice composition does notcomprise zinc inorganic salts such as zinc chloride or zinc sulphate,due to the unpleasant, astringent mouthfeel that the free zinc ionsimparted.

Glycine

The dentifrice compositions of the present invention comprise glycine.The glycine can be present in its free form or suitable salts form.Suitable salts include salts known in the art to be pharmaceuticallyacceptable salts considered to be physiologically acceptable in theamounts and concentrations provided.

Preferably the glycine is present in the amount of from about 0.1% toabout 6%, by weight of the composition. Preferably, the glycine ispresent in the amount of from about 0.5% to about 5%, more preferablyfrom about 0.8% to about 4%, by weight of the composition.

It has been surprisingly discovered that the presence of glycine in azinc containing formulation help to increase the penetration depthand/or penetration rate of zinc ion into the biofilms. Further, the useof glycine improves the sensorial experience by reducing the associatedastringency and metallic taste of zinc that will ensure productcompliance and usage habit to deliver the oral health benefits.Moreover, without wishing to be bound by theory, the presence of glycinemay further lead to improved delivery of the fluoride ions source to thetooth surface, as a result of the destabilized dental biofilm, whichcould further aid with the enamel remineralization cycle.

Fluoride Ions

Preferably, the dentifrice compositions comprise a fluoride ion sourceas anti-caries agent. Suitable examples of fluoride ions may be selectedfrom a source comprising stannous fluoride, sodium fluoride, potassiumfluoride, sodium monofluorophosphate (“MFP”), indium fluoride, aminefluoride, zinc fluoride, and mixtures thereof. Preferably, the fluorideion source is selected from sodium fluoride, stannous fluoride, MFP, orcombinations thereof. The fluoride ion source may be present in anamount of from 0.0025% to 5%, or from 0.05% to 4%, or from 0.1% to 2%,or preferably from 0.2% to 1.5%, by weight of the composition, toprovide anti-caries effectiveness. In certain examples, the fluoride ionsource can be present in an amount sufficient to provide fluoride ionsconcentration in the composition at levels from 25 ppm to 25,000 ppm,generally at least from 500 ppm to 1600 ppm, for example 1100 ppm or1450 ppm. The appropriate level of fluoride will depend on theparticular application. A toothpaste for general user would typicallyhave about 1000 ppm to 1500 ppm, with pediatric toothpaste havingsomewhat less.

Other Active Agents

The dentifrice compositions of the present invention may comprise astannous ion source. In some examples, the stannous ion source may bepresent in the amount of from about 0.01% to about 5%, preferably fromabout 0.05% to about 4%, or more preferably from about 0.1% to about 2%,by weight of the composition, to provide anti-bacterial effectiveness.The stannous ion source used herein may include any safe and effectivestannous salt. Suitable examples of stannous ion source are selectedfrom the group consisting of stannous chloride, stannous fluoride,stannous acetate, stannous gluconate, stannous oxalate, stannoussulfate, stannous lactate, stannous tartrate, stannous iodide, stannouschlorofluoride, stannous hexafluorozirconate, stannous citrate, stannousmalate, stannous glycinate, stannous carbonate, stannous phosphate,stannous pyrophosphate, stannous metaphosphate, and combinationsthereof. Preferably, the stannous ion source is selected from stannousfluoride, stannous chloride, and combinations thereof. In one preferredexample, the stannous ion source comprises stannous chloride. In anotherpreferred example, the stannous ion source comprises stannous fluoride.

Alternatively, the dentifrice composition is substantially free ofstannous ion source, preferably essentially free of stannous ion source,more preferably free of stannous ion source.

The dentifrice compositions of the present invention may optionally alsoinclude other anti-bacterial agents, preferably present in an amount offrom 0.035% or more, from 0.05% to 2%, from 0.1% to 1%, by weight of thecomposition. Examples of these other anti-bacterial agents may includenon-cationic anti-bacterial agents such as, for example, halogenateddiphenyl ethers, phenolic compounds including phenol and its homologs,mono and poly-alkyl and aromatic halophenols, resorcinol and itsderivatives, xylitol, bisphenolic compounds and halogenatedsalicylanilides, benzoic esters, and halogenated carbanilides. Otheruseful anti-bacterial agents are enzymes, including endoglycosidase,papain, dextranase, mutanase, and combinations thereof.

pH

The pH of the dentifrice composition of the present invention may befrom pH 5.0 to 10.5, preferably from 5.5 to 8.0, more preferably from6.0 to 7.8. In some preferred examples, the pH of the dentifricecompositions may be from pH 5.5 to 8.5. Alternatively, the dentifricecomposition may have a pH of from 6 to 9, or from 6.5 to 8. In someexamples, the pH is from 5.5 to 7.8, alternatively from pH 6.0 to pH7.5, e.g., pH 7.7, or pH 7.6, or pH 7.5, or pH 7.4, or pH 7.3, or pH7.2, or pH 7.1, or pH 7.0, or pH 6.9, or pH 6.8, or pH 6.7, or pH 6.6,or pH 6.5, or pH 6.4, or pH 6.3, or pH 6.2, or pH 6.1, or pH 6.0, or pH5.9, or pH 5.8, or pH 5.7, or pH 5.6, or pH 5.5.

The pH is typically measured using a ratio of 1:3 of paste:water,whereby 1 gram of the dentifrice composition (e.g., toothpaste) is mixedinto 3 grams of deionized water, and then the pH is assessed with anindustry accepted pH probe that is calibrated under ambient conditions.The pH is measured by a pH meter with Automatic Temperature Compensating(ATC) probe. For purposes of clarification, although the analyticalmethod describes testing the dentifrice composition when freshlyprepared, for purposes of claiming the present invention, the pH may betaken at any time during the product's reasonable lifecycle (includingbut not limited to the time the product is purchased from a store andbrought to the user's home).

After each usage the electrode should be washed free from the samplesolution with water. Remove any excess water by wiping with a tissue,such as Kimwipes or equivalent. When electrode is not in use, keepelectrode tip immersed in pH 7 buffer solution or electrode storagesolution. Equipment details are as follows:

-   -   pH Meter: Meter capable of reading to 0.01 or 0.001 pH units.    -   Electrode: Orion Ross Sure-Flow combination: Glass body—VWR        #34104-834/Orion #8172BN or VWR #10010-772/Orion #8172BNWP.        -   Epoxy body—VWR #34104-830/Orion #8165BN or VWR            #10010-770/Orion #8165BNWP.        -   Semi-micro, epoxy body—VWR #34104-837/Orion #8175BN or VWR            #10010-774/Orion #3175BNWP.        -   Orion PerpHect combination: VWR #34104-843/Orion #8203BN            semi-micro, glass body.    -   ATC Probe: Fisher Scientific, Cat. #13-620-16.

pH Modifying Agent

The dentifrice compositions herein may optionally include an effectiveamount of a pH modifying agent, alternatively wherein the pH modifyingagent is a pH buffering agent. The pH modifying agents, as used herein,refer to agents that can be used to adjust the pH of the dentifricecompositions to the above-identified pH range. The pH modifying agentsinclude hydrochloric acid, alkali metal hydroxides, ammonium hydroxide,organic ammonium compounds, carbonates, sesquicarbonates, borates,silicates, phosphates, imidazole, and mixtures thereof.

Specific pH modifying agents include monosodium phosphate (monobasicsodium phosphate), trisodium phosphate (sodium phosphate tribasicdodecahydrate or TSP), sodium benzoate, benzoic acid, sodium hydroxide,potassium hydroxide, alkali metal carbonate salts, sodium carbonate,imidazole, pyrophosphate salts, polyphosphate salts both linear andcyclic form, sodium gluconate, lactic acid, sodium lactate, citric acid,sodium citrate, phosphoric acid.

Thickening Agent

The dentifrice compositions of the present invention may comprise athickening agent. Preferably the dentifrice composition comprises from0.1% to 5%, preferably from 0.8% to 3.5%, more preferably from 1% to 3%,yet still more preferably from 1.3% to 2.6%, by weight of thecomposition, of the thickening agent.

Preferably the thickening agent comprises a thickening polymer, athickening silica, or a combination thereof. Yet more preferably, whenthe thickening agent comprises a thickening polymer, the thickeningpolymer is selected from a charged carboxymethyl cellulose, a non-ioniccellulose derivative, a linear sulfated polysaccharide, a natural gum,polymers comprising at least a polycarboxylated ethylene backbone, andcombinations thereof.

In one example the thickening silica is obtained from sodium silicatesolution by destabilizing with acid as to yield very fine particles. Onecommercially available example is ZEODENT® branded silicas from HuberEngineered Materials (e.g., ZEODENT® 103, 124, 113 115, 163, 165, 167).

Preferably the linear sulfated polysaccharide is a carrageenan (alsoknown as carrageenin). Examples of carrageenan includeKappa-carrageenan, Iota-carrageenan, Lambda-carrageenan, andcombinations thereof.

In one example the CMC is prepared from cellulose by treatment withalkali and monochloro-acetic acid or its sodium salt. Differentvarieties are commercially characterized by viscosity. One commerciallyavailable example is Aqualon™ branded CMC from Ashland SpecialIngredients (e.g., Aqualon™ 7H3SF; Aqualon™ 9M3SF Aqualon™ TM9A;Aqualon™ TM12A).

Preferably a natural gum is selected from the group consisting of gumkaraya, gum arabic (also known as acacia gum), gum tragacanth, xanthangum, and combination thereof. More preferably the natural gum is xanthangum. Xanthan gum is a polysaccharide secreted by the bacteriumXanthomonas camestris. Generally, xanthan gum is composed of apentasaccharide repeat units, comprising glucose, mannose, andglucuronic acid in a molar ratio of 2:2:1, respectively. The chemicalformula (of the monomer) is C₃₅H₄₉O₂₉. In one example, the xanthan gumis from CP Kelco Inc (Okmulgee, US).

Preferably, the non-ionic cellulose or derivative thereof has an averagemolecular weight range of 50,000 to 1,300,000 Daltons, and preferably anaverage degree of polymerization from 300 to 4,800. More preferably, thenon-ionic cellulose or derivative thereof is hydroxyethyl cellulose(“HEC”).

Preferably the polymer comprising at least a polycarboxylated ethylenebackbone is selected from the group consisting of: co-polymers of maleicanhydride with methyl vinyl ether having a molecular weight of 30,000 to1,000,000 Daltons; homo-polymers of acrylic acid; and co-polymers ofmaleic acid and acrylic acid or methacrylic.

The co-polymers of maleic anhydride with methyl vinyl ether are at leastone of: Gantrez AN139 (M.W. 500,000 Daltons), Gantrez AN119 (M.W.250,000 Daltons), or S-97 Pharmaceutical Grade (M.W. 70,000 Daltons);and the homo-polymers of acrylic acid and co-polymers of maleic acid andacrylic acid or methacrylic acid are at least one of: Acusol 445, Acusol445N, Acusol 531, Acusol 463, Acusol 448, Acusol 460, Acusol 465, Acusol490, Sokalan CP5, Sokalan CP7, Sokalan CP45, or Sokalan CP12S; and (v)combinations thereof.

In an example, the GANTREZ™ series of polymers are co-polymers of maleicanhydride with methyl vinyl ether having a molecular weight (M.W.) of30,000 Daltons to 1,000,000 Daltons. These co-polymers are available forexample as GANTREZ™ AN139 (M.W. 500,000 Daltons), AN119 (M.W. 250,000Daltons) and S-97 Pharmaceutical Grade (M.W. 70,000 Daltons), fromAshland Chemicals (Kentucky, USA).

In another example, the ACUSOL™ and the SOKALAN series of polymersinclude homopolymers of acrylic acid and copolymers of maleic acid andacrylic acid or methacrylic. Examples are 0:1000 to 1000:0 copolymers ofmaleic acid with acrylic acid having a molecular weight (M.W.) of about2,000 to about 1,000,000. These copolymers are commercially available asACUSOL™ 445 and 445N, ACUSOL™ 531, ACUSOL™ 463, ACUSOL™ 448, ACUSOL™460, ACUSOL™ 465, ACUSOL™ 497, ACUSOL™ 490 from Dow Chemicals (Michigan,USA) and as Sokalan® CP 5, Sokalan® CP 7, Sokalan® CP 45, and Sokalan®CP 12 S from BASF (New Jersey, USA).

In another example, the crosslinked polyacrylic acid (PAA) polymer is ageneric term for the synthetic high molecular weight polymers of acrylicacid. These may be homopolymers of acrylic acid, crosslinked with anallyl ether pentaerythritol, allyl ether of sucrose or allyl ether ofpropylene. And, in a water solution at neutral pH, PAA is an anionicpolymer, i.e. many of the side chains of PAA will lose their protons andacquire a negative charge. Carbopol®-type polymers, such as Carbopol®,Pemulen® and Noveon®, are polymers of acrylic acid, crosslinked withpolyalkenyl ethers or divinyl glycol. Carbomer commercial codes, e.g.940™, indicate the molecular weight and the specific components of thepolymer.

Humectants

The dentifrice compositions herein may include humectants present in theamount of from 0% to 70%, or from 15% to 55%, by weight of thecompositions. Humectants keep dentifrice compositions from hardeningupon exposure to air and certain humectants may also impart desirablesweetness of flavor to dentifrice compositions. Suitable examples ofhumectants may include glycerin, sorbitol, polyethylene glycol,propylene glycol, xylitol, trimethyl glycine, and mixtures thereof.Other examples may include other edible polyhydric alcohols. In someexamples, the humectant is selected from sorbitol, glycerin, andcombinations thereof. In a preferred example, the humectant is sorbitol.In another preferred example, the humectant is glycerin. In an example,the composition comprises from 10% to 66%, alternatively from 30% to55%, of humectant by weight of the composition.

Water

Water is commonly used as a carrier material in dentifrice compositionsdue to its many benefits. For example, water is useful as a processingaid, is benign to the oral cavity and assists in quick foaming oftoothpastes. Water may be added as an ingredient in its own right or itmay be present as a carrier in other common raw materials such as, forexample, sorbitol and sodium lauryl sulfate.

In some examples, the dentifrice compositions herein may include from10% to 70%, or preferably from 15% to 30%, by weight of the composition,of total water content. The term “total water content” as used hereinmeans the total amount of water present in the dentifrice composition,whether added separately or as a solvent or carrier for other rawmaterials but excluding that which may be present as water ofcrystallization in certain inorganic salts. Preferably, the water is USPwater.

Alternatively, in other examples, the dentifrice compositions herein mayinclude from 0% to 5%, by weight of the composition, of total watercontent. For example, the dentifrice composition may be substantiallyfree of water, preferably free of water.

Surfactants

Optionally, but preferably, the dentifrice compositions comprise asurfactant. The surfactant may be selected from anionic, nonionic,amphoteric, zwitterionic, cationic surfactants, or combinations thereof,preferably the surfactant is anionic, more preferably the anionicsurfactant is sodium lauryl sulfate (SLS). An example of a zwitterionicsurfactant is cocamidopropyl betaine. The dentifrice composition maycontain one, two, or more surfactants. The composition may include asurfactant at a level of from 0.1% to 20%, preferably from 1% to 10%, byweight of the total composition.

Abrasives

The dentifrice composition comprises an effective amount of an abrasive.Examples of abrasives include a calcium-containing abrasive, a silica,or combinations thereof. If containing a calcium-containing abrasive,the calcium-containing abrasive is preferably selected from the groupconsisting of calcium carbonate, dicalcium phosphate, tricalciumphosphate, calcium orthophosphate, calcium metaphosphate, calciumpolyphosphate, calcium oxyapatite, sodium carbonate, sodium bicarbonate,and combinations thereof. If a silica, preferably the silica is aprecipitated silica (e.g., sodium silicate solution by destabilizingwith acid as to yield very fine particles) such as those from theZEODENT® series from Huber Engineered Materials (e.g., ZEODENT® 103,124, 113 115, 163, 165, 167). It is acknowledged that some of thesesilicas (e.g., synthetic amorphous silica) can perform both abrasive andthickening functions, but are included herein under the term “abrasive”for purposes of the present invention. Preferably the dentifricecomposition comprises from 1% to 35%, more preferably from 5% to 25% ofabrasive, by weight of the composition.

Flavoring Agent

The dentifrice composition herein may include from 0.01% to 5%,preferably from 0.1% to 2%, by weight of the composition, of a flavoringagent. Examples of suitable flavoring agent that may be used in thedentifrice composition include those described in U.S. Pat. No.8,691,190; Haught, J. C., from column 7, line 61 to column 8, line 21.In some examples, the flavoring agent may be selected from methylsalicylcate, menthol, eugenol and cineol. In some examples, thedentifrice composition may comprise a flavor mixture which is free of orsubstantially free of methyl salicylcate, menthol, eugenol and cineol.

Sweetener

The dentifrice compositions herein may include a sweetening agent. Thesweetening agent is generally present in the dentifrice compositions atlevels of from 0.005% to 5%, by weight of the composition. Suitableexamples of sweetener include saccharin, dextrose, sucrose, lactose,xylitol, maltose, levulose, aspartame, sodium cyclamate, D-tryptophan,dihydrochalcones, acesulfame, sucralose, neotame, and mixtures thereof.Other suitable examples of sweetener are described in U.S. Pat. No.8,691,190; Haught, J. C. from column 9, line 18 to column 10, line 18.

Coloring Agents

The dentifrice compositions herein may include a coloring agent presentin the amount of from 0.001% to 0.01%, by weight of the compositions.The coloring agent may be in the form of an aqueous solution, preferably1% coloring agent in a solution of water. Suitable examples of coloringagents may include pigments, pealing agents, filler powders, talc, mica,magnesium carbonate, calcium carbonate, bismuth oxychloride, zinc oxide,and other materials capable of creating a visual change to thedentifrice compositions. Other suitable examples may include titaniumdioxide (TiO₂). Titanium dioxide is a white powder which adds opacity tothe compositions and is generally present in the dentifrice compositionsat levels of from 0.25% to 5%, by weight of the composition.

Other Ingredients The present dentifrice composition can comprise theusual and conventional ancillary components that are known to oneskilled in the art. Optional ingredients include, for example, but arenot limited to, anti-plaque agent, anti-sensitivity agent, whitening andoxidizing agent, anti-inflammatory agent, anti-calculus agent, chelatingagent, tooth substantive agent, analgesic and anesthetic agent. It willbe appreciated that selected components for the dentifrice compositionsmust be chemically and physically compatible with one another.

EXAMPLES

The following examples and descriptions further clarify embodimentswithin the scope of the present invention. These examples are givensolely for the purpose of illustration and are not to be construed aslimitations of the present invention as many variations thereof arepossible without departing from the spirit and scope.

Example A: Examples 1 to 3

Examples 1 is a reference to the Phosphate Buffer Solution, whereas Ex.2 and Ex. 3 are dentifrice compositions. They may be suitably preparedby conventional methods chosen by the formulator. Example 2 is acomparative formulation and example 3 is an inventive compositioncomprising zinc lactate and glycine. All of the compositions areprepared by admixture of the components in Table 1, in the proportionsindicated.

TABLE 1 Examples 1 to 3 Amount (Wt %) Ex. 2 Ex. 3 Ingredients Ex. 1(Comparative) (Inventive) Sorbitol Solution 70% — 40.50 40.50 SodiumFluoride — 0.321 0.321 Zinc Lactate Dihydrate — 1.10 1.10 Zinc Citrate —— — Glycine — — 2.00 Hydroxyethyl Cellulose — 0.30 0.30 CarrageenanMixture Iota — 0.50 0.50 Sodium CMC — 1.00 1.00 Silica Abrasive — 20.0020.00 Sodium Lauryl Sulphate — 7.50 7.50 (28% soln.) Sodium Saccharin —0.40 0.40 Flavor/sensate oils — 1.30 1.30 Sodium Citrate — 0.274 0.274Sodium Hydroxide — — 0.125 Water and minors — q.s. q.s. (e.g., colorsoln.) NaCl 0.800 — — KCl 0.020 — — Na2HPO4 0.142 — — KH2PO4 0.024 — —Warer 99.014 — — Total 100% 100% 100% Target pH 7.0 6.7 7.3

Example B—Assay for Measuring Biofilm Architecture, Penetration ofAnti-Bacterial Agent & Endotoxin Neutralization in the Biofilms

The following assay is used an in situ plaque biofilm for inventivedentifrice compositions of the present invention and controls in orderto: (1) assess the biofilm EPS matrix destabilization and thickness ofthe dental biofilm by measuring fluorescent light emitted from thelabeled EPS biofilm; and (2) assess penetration efficiency of zinc ionswith bacteria via measurement of co-localization percentage.

Details of the assay are described below.

(a) Substrate for Biofilm Growth

Hydroxyapatite (“HA”) disks are used for in situ growth of biofilms. TheHA disks are designed having three parallel grooves (i.e., 200 μm wide;200 μm deep for two sides' grooves; while 500 μm wide and 500 μm deepfor the middle groove) in each disk. When attaching disks to subject'smouth, keep these grooves vertical, to mimic interproximal gap betweenteeth, which is the hard-to-clean area where plaque generally tends toaccumulate. This model allows the collection of undisturbed plaque fromthe grooves. HA disks are manufactured by Shanghai Bei'erkangbiomedicine limited company (Shanghai, China).

(b) Wearing the Splint

Human subjects wear the splint. Each subject wears up to 12 HA disks onthe splint to ensure that, at least, 9 HA disks are available after 48hours. A non-limiting example of such a splint and HA disks are shown inFIG. 1. With reference to FIG. 1, the device (1) holds a plurality of HAdisks (2 a-2 d). In a specific example, and with reference to FIG. 2,the HA disk (201) has three parallel grooves (203) (the two sides'grooves (203 a and 203c) are 300 μm wide and 300 μm deep; while themiddle grove (203 b) (in between the two side grooves) is 500 μm wideand 500 μm deep). The middle groove is designed wider and deeper thanthe two sides' grooves so that the HA disk can be more easily separatedinto two identical half-disks for head-to-head comparison purposes. FIG.3 is a schematic of a cross-sectional view of the groove (2003) withbiofilm (2005) therein. Further details of the HA disks are described inUS2017/0056531 (e.g. paragraphs [0019]-[0020]).

Although not shown in FIG. 3, the disks can be positioned such that therecede is in the inter-dental space between the teeth (since thislocation is prone to plaque (given the difficulty in cleaning, etc.)).The subjects withdraw the splint only during meals (the splint stored inan opaque container in humid conditions) and to perform oral hygieneprocedures Immediately thereafter, the splint is worn again. Subjectsare asked to use a straw when drinking.

(c) In-situ Biofilms Release from HA Desk

All HA disks are removed from the splint at 48 hours by tweezers.Tweezers are used to hold the edge of HA chips and transfer the HA diskto a 2 mL centrifuge tube containing PBS (phosphate buffered saline)solution. Tweezers are washed thoroughly (water; 75% alcohol; and thendeionized water) before every disk transfer.

(d) Preparation of Toothpaste Supernatant

15 grams of deionized water is added to 5 grams toothpaste (using anyone of the Examples 1-3). After stirring thoroughly, the mixture iscentrifuge at 12,000 RPM for 20 minutes. The supernatant is prepared oneday before usage and stored at 4° C.

(e) Confocal Laser Scanning Microscopy

After the HA disks are removed from the splint. The HA disks are usedfor ex vivo treatment by the different inventive and comparativecompositions. After being treated with the subject supernatant andlabeled with microbial fluorescent probe and stannous fluorescent probe(such as described in US2018/0072944A1; Shi et al.), the biofilms in thegrooves are measured by confocal laser scanning microscopy (“CLSM”) (asdescribed below).

(f) Disk Preparation

The HA disks are rinsed in PBS solution and each HA disk is divided intotwo halves by tweezers. Thereafter, each half-disk is placed into500-1000 μL of PBS solution statically for 1 minute. Each disk istreated for two minutes by either PBS solution or toothpastesupernatant. Each disk is washed by holding each disk with tweezers,shaken for ten rounds of back and forth in 1 mL of PBS solution, andthen this washing cycle is repeated. Then each disk is immersed into500-1000 μL PBS solution statically for 5 minutes.

After being treated with PBS and/or the oral care composition (e.g.,toothpaste) supernatant and labeled with specific fluorescent probes,the biofilm in the grooves is measured by confocal laser scanningmicroscopy (CLSM).

(g) Fluorescence Probe Staining and Microscopy

“Ion fluorescent probe” means a fluorescent probe that specificallybinds to one kind of ions and emit fluorescence at a certain wavelength.In recent years, significant emphasis has been placed on the developmentof new, highly selective fluorescent probes of ions because of theirpotential applications in biochemistry and environmental research. Manykinds of signaling mechanisms have been proposed and utilized foroptical detection of ions, including photo-induced electron/energytransfer (PET), intramolecular charge transfer (ICT), fluorescenceresonance energy transfer (FRET), and so on. Some of these fluorescentprobes can also be applied in fluorescence bioimaging, which causeslittle cell damage and is highly sensitive with high-speed spatialanalysis of living cells. Specifically, FRET imaging that affordssimultaneous recording of two emission intensities at differentwavelengths in the presence and absence of analytes has provided afacile method for visualizing complex biological processes at themolecular level. This technique appears to be suited to the study ofphysiological functions or pathogenesis of ions in biofilm and humanbody.

Zinc penetration efficiency of zinc ions with bacteria via measurementof co-localization percentage. Non-limiting examples of a zincfluorescent probe suitable for labeling the biofilm may include any onefollowing of the compounds:

2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-diaminospiro[isoindoline-1,9′-xanthen]-3-one);(b)2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-bis(ethylamino)-2′,7′-dimethylspiro[isoindoline-1,9′-xanthen]-3-one);(c)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one;(d)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one;(e)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-bis(phenylamino)spiro[isoindoline-1,9′-xanthen]-3-one;(f)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-di(pyrrolidin-1-yl)spiro[isoindoline-1,9′-xanthen]-3-one;(g)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-diamino-2′,7′-diethylspiro[isoindoline-1,9′-xanthen]-3-one;(h)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-2′,7′-dibutyl-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one)-3-one;(i)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-dimorpholinospiro[isoindoline-1,9′-xanthen]-3-one;(j)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-di(piperidin-1-yl)spiro[isoindoline-1,9′-xanthen]-3-one;(k)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-1′,2′,3′,4′,8′,9′,10′,11′-octahydrospiro[isoindoline-1,6′-pyrano[3,2-g:6,6-g′]diquinolin]-3-one;(l)2-(2-(((1H-pyrrol-2-yl)methyl)amino)ethyl)-1′,2′,3′,4′,10′,11′,12′,13′-octahydrospiro[isoindoline-1,7′-pyrano[2,3-f:6,5-f′]diquinolin]-3-one;(m)2-(2(((1H-pyrrol-2-yl)methyl)amino)ethyl)-2′,7′-dimethyl-3′,6′-di(piperidin-1-yl)spiro[isoindoline-1,9′-xanthenl]-3-one)and (n)2-(2(bis((1H-pyrrol-2-yl)methyl)amino)ethyl)-3′,6′-bis(diethylamino)spiro[isoindoline-1,9′-xanthen]-3-one).

Generally these zinc fluorescent probes contain a Rhodamine B derivativemoiety as fluorophore, linked via amide moiety to 2-methyl 1H-pyrrole.Further details are described in the WO 2016/041138 A1.

The “Microbial fluorescent probe” means a fluorescent probe that bindsto microbes of a biofilm and emit fluorescence at a certain wavelength.One class of such probes includes fluorescently labeledoligonucleotides, preferably rRNA-directed oligonucleotides.Non-limiting examples include SYTO™ branded dyes. One specific exampleis SYTO® 9 Green Fluorescent Nucleic Acid Stain, wherein excitation is a485 (DNA) and 486 (RNA), and light emission is detected at 498 (DNA) and501 (RNA).

After treatment and immersing, each half-disk is stained with the Znprobe together with Syto-9 probe (containing 5 μM Syto-9 and 5 μM Znprobe) for 30 minutes in the dark. The SYTO-9/Zn dye stained samples,the following parameters are used: λex=488 nm/560 nm, λem=500/580 nm,20× objective lens, and scanning from bottom of surface bacteria for 60μm with step size=3 μm.

Fluorescence labeled calcium probes are molecules that exhibit anincrease in fluorescence upon binding Ca²⁺. The biofilm is labeled witha calcium fluorescent probe. Examples of a calcium fluorescent probesuitable for labeling the biofilm may be any one or more of thefollowing compounds:

-   (a) Fluo-3™, AM™, cell permeant fluorescence stains;-   (b) Fluo-3™, Pentapotassium Salt, cell impermeant fluorescence    stains;-   (c) Fluo-4™, AM™, cell permeant fluorescence stains;-   (d) Fluo-4™, Pentapotassium Salt, cell impermeant fluorescence    stains;-   (e) Fluo-4 Direct™ Calcium Assay Kit;-   (f) Mag-Fluo-4™, Tetrapotassium Salt, cell impermeant fluorescence    stains; and-   (g) Fluo-5F™, AM™, cell permeant fluorescence stains.    One or more of these probes may be available from ThermoFisher    Scientific Company, Waltham, Mass.

Fluo-3™ is used to image the spatial dynamics of Ca2+ signaling. Biofilmmay be treated with the AM™ ester forms of calcium probes by adding thedissolved probe directly to biofilm. Fluo-3™, AM™, cell permeantfluorescent probes are used for intracellular and extracellular calciumstaining using confocal microscopy, flow cytometry, and microplatescreening applications (absorption/emission maxima ˜506/526 nm). It isreported that the Concanavalin A™ (Con A), Alexa Fluor® 594 Conjugate isa reliable alternative to stain EPS of biofilm. Alexa Fluor® 594conjugate of Con A exhibits the bright, red fluorescence of the AlexaFluor® 594 dye (absorption/emission maxima ˜590/617 nm). ConcanavalinA™, Alexa Fluor® 594 Conjugate selectively binds to a-mannopyranosyl andα-glucopyranosyl residues which are rich in EPS part of biofilm.

One specific example is Concanavalin A™, Fluorescein Conjugate™, whereinexcitation is 494 nm, and maximum light emission is detected at 518 nm.These EPS fluorescent probes are widely available as well as theprocedure details in how to use them to quantitatively determine thelocation and/or amount of EPS.

Examples of an EPS fluorescent probe suitable for labeling the biofilmmay be any one of the following compounds:

-   (a) Molecular Probes™ Concanavalin A™ Alexa Fluor® 350 Conjugate™;-   (b) Molecular Probes™ Concanavalin A™ Alexa Fluor® 488 Conjugate™;-   (c) Molecular Probes™ Concanavalin A™ Alexa Fluor® 594 Conjugate™;-   (d) Molecular Probes™ Concanavalin A™ Alexa Fluor® 633 Conjugate™;-   (e) Molecular Probes™ Concanavalin A™ Alexa Fluor® 647 Conjugate™;-   (f) Molecular Probes™ Concanavalin A™ Fluorescein Conjugate™;-   (g) Molecular Probes™ Concanavalin A™ Oregon Green® 488 Conjugate™;-   (h) Molecular Probes™ Concanavalin A™ tetramethylrhodamine    Conjugate™;-   (i) Molecular Probes™ Concanavalin A™ Texas Red® Conjugate™    One or more of these probes may be available from ThermoFisher    Scientific Company, Waltham, Mass.

After treatment and immersing, each half-disk specimen is stained with adye mixture solution of the Fluo-3™, AM™, cell permeant fluorescentprobe together with Concanavalin A™, Alexa Fluor® 594 Conjugate probe(containing 5 uM Fluo-3™+5 uM Con-A™ ) for 30 minutes in the dark. Afterstaining, each specimen is immersed into 500-1000 ul PBS solutionstatically for 2 minutes.

(h) Confocal Laser Scanning Microscopy

The Leica™ TCS SP8 AOBS spectral confocal microscope is used. Theconfocal system consists of a Leica™ DM6000B upright microscope and aLeica™ DMIRE2 inverted microscope. An upright stand is used forapplications involving slide-mounted specimens; whereas the invertedstand, having a 37° C. incubation chamber and CO₂ enrichmentaccessories, provides for live cell applications. The microscopes sharean exchangeable laser scan head and, in addition to their ownelectromotor-driven stages, a galvanometer-driven high precision Z-stagewhich facilitates rapid imaging in the focal (Z) plane. In addition toepifluorescence, the microscopes support a variety of transmitted lightcontrast methods including bright field, polarizing light anddifferential interference contrast, and are equipped with 5×, 20×, 40×,63× (oil and dry) and 100× (oil) Leica™ objective lenses.

The laser scanning and detection system is described. The TCS SP8 AOBSconfocal system is supplied with four lasers (one diode, one argon, andtwo helium neon lasers) thus allowing excitation of a broad range offluorochromes within the UV, visible and far red ranges of theelectromagnetic spectrum. The design of the laser scan head, whichincorporates acousto-optical tunable filters (“AOTF”), anacousto-optical beam splitter (“AOBS”) and four prism spectrophotometerdetectors, permits simultaneous excitation and detection of threefluorochromes. The upright microscope also has a transmission lightdetector making it possible to overlay a transmitted light image upon afluorescence recording.

Leica™ Confocal software LAS AF3.3.0 is used. The confocal is controlledvia a standard Pentium PC equipped with dual monitors and running Leica™Confocal Software. The Leica Confocal Software LAS AF3.3.0 (availablefrom Leica Lasertechnik GmbH, Heidelberg, Germany) provides an interfacefor multi-dimensional image series acquisition, processing and analysis,that includes 3D reconstruction and measurement, physiological recordingand analysis, time-lapse, fluorochrome co-localization, photo-bleachingtechniques such as FRAP and FRET, spectral immixing, and multicolourrestoration.

(i) Image Analysis

Zn Analysis; The SYTO-9/Zn dye stained samples are chosen to quantifyoverlap efficiency of red and green pixels. Using the software, thepixel overlap of “green” bacterial probes and that of “red” zinc probesare identified, and then this value is divided by all non-black pixels(that include non-overlapping stannous probes) to provide aco-localization percentage of stannous in bacteria. Generally, thehigher this co-localization percentage, the more efficacious the oralcare product is in delivering zinc into bacteria.

Ca:EPS; The Fluo-3™/Con-A™ stained specimens, both fluorescence channelsare chosen to quantify fluorescence intensity ratio of green pixels(Calcium) to red pixels (EPS) and Con-A™ fluorescence channel is chosento measure the biofilm thickness. Whereby, six selected fields of Con-A™fluorescence channel of each specimen are evaluated. These fields areconsidered as representative of the whole sample after the observer'sgeneral examination. The distance is measured from the surface of thebiofilm to its base, measuring the thickness of the field, andsubsequently the mean thickness of the biofilm of the correspondingspecimen is calculated.

Results: Subjects are treated with the Inventive Composition Ex. 3(i.e., zinc lactate+2% Glycine), Comparative Composition Ex. 2 (i.e.,zinc lactate only), an Commercial product Composition Ex. 4 (i.e.,Colgate Total™ Whole Mouth Health, Daily Repair toothpaste, containingZinc Citrate/Zinc Oxide+Arginine), and Control Ex. 1 (PBS) as negativecontrol. The results are provided in Table 2.

TABLE 2 Active Penetration Rate in Biofilm Biofilm Zn Total Soluble ZnThickness Penetration Zinc Zinc Recovery Examples (um) (%) (ppm) (ppm)(%) Ex. 1 Phosphate 35.52 — — — — Buffer Solution (artificial saliva)Ex. 2 Zinc Lactate 13.37 62.58 2500 545 83 Ex. 3 Zinc Lactate + 7.1480.01 2500 510 78 Glycine Ex. 4 Zinc 16.755 76.50 9300 1054 11Citrate/Oxide + Arginine *Ex. 4 is a commercial product composition(Colgate Total ™ Whole Mouth Health, Daily Repair toothpaste)

Data is discussed. In reference to Table 2, the fluorescence intensityof Zn within in situ plaque biofilm and average biofilm thickness aremeasured for various examples and toothpaste formulations are provided.The first column of Table 2 identifies the product with key actives. Inturn, each product includes the examples described in Table 1 above(namely examples 2-3) as well as one commercialized products examples 4.Notably example 4 contains zinc citrate and zinc oxide as zinc ionsource, and 1.5% of Arginine - - - a basic amino acid. The second columnof Table 2 indicates the dental biofilm thickness. The lower the biofilmthickness, the more effective is the composition. The third columnindicates the zinc penetration (%). The higher the percentage, the moreeffective is the zinc penetration into the biofilm. The fourth and fifthcolumns indicate the total zinc amount (ppm) and the soluble zinc amount(ppm) present in the examples, respectively. The soluble zinc amount ismeasured when diluting the example into 3 times of water.

Still referring to Table 2, example 1 (“Ex 1”) Phosphate Buffer Solution(“PBS”) is used as the negative control. Accordingly, Ex 1 is the leasteffective (compared to the other compositions) on the impact on dentalbiofilm thickness. Inventive Ex. 3 shows significantly reduced biofilmthickness and significantly increased zinc penetration compared to thecomparative Ex. 2. Notably, Inventive Ex. 3 (containing 2% glycine) evenshowed significant reduced biofilm thickness, compared with thecommercial product Ex. 4 which contains much higher amount of zinc ion,as well as basic amino acid arginine (1.5%).

Example C: Consumer Sensory Test

Consumer Sensory Tests are conducted to measure the preference ofconsumer towards the Inventive Example 3 vs. the comparative Example 2.

18 trained sensory panelists are instructed for use of a series testproduct with unawareness of the product identity i.e. brand,ingredients, etc. they are asked to brush teeth using a pairedcomparison products (2 vs. 3) with randomized brushing order. Eachassigned toothpaste is dispensed upon an Oral B Navigator brush andbrushed for a controlled 2 minutes, with each panelist recording thesensorial attributes (i.e. regarding astringency) on the standardquestionnaire with a 1 to 5 grading score. Table 3 shows the averageranking for Examples 2 and 3. It can clearly showed that addition of theglycine to zinc lactate significantly reduces the noticeable astringencyof the dentifrice with 90% confidence level.

TABLE 3 Sensory Results Sensory Panel Grading Ex. 2 Ex. 3 Zinc LactateZinc Lactate + Glycine Astringency post brushing 4 3 *highly astringency5; mild astringency 3; no astringency 0

The dimensions and values disclosed herein are not to be understood asbeing strictly limited to the exact numerical values recited. Instead,unless otherwise specified, each such dimension is intended to mean boththe recited value and a functionally equivalent range surrounding thatvalue. For example, a dimension disclosed as “40 mm” is intended to mean“about 40 mm.”

Every document cited herein, including any cross referenced or relatedpatent or application and any patent application or patent to which thisapplication claims priority or benefit thereof, is hereby incorporatedherein by reference in its entirety unless expressly excluded orotherwise limited. The citation of any document is not an admission thatit is prior art with respect to any invention disclosed or claimedherein or that it alone, or in any combination with any other referenceor references, teaches, suggests or discloses any such invention.Further, to the extent that any meaning or definition of a term in thisdocument conflicts with any meaning or definition of the same term in adocument incorporated by reference, the meaning or definition assignedto that term in this document shall govern.

While particular embodiments of the present invention have beenillustrated and described, it would be obvious to those skilled in theart that various other changes and modifications can be made withoutdeparting from the spirit and scope of the invention. It is thereforeintended to cover in the appended claims all such changes andmodifications that are within the scope of this invention.

What is claimed is:
 1. A dentifrice composition, comprising: a) from0.2% to 2.0%, by weight of the composition, of a zinc lactate; b) fromabout 0.1% to about 6%, by weight of the composition, of a glycine orsalt thereof; and c) from 0.05% to 0.5%, by weight of the composition,of a fluoride ion.
 2. The dentifrice composition according to claim 1,wherein the dentifrice composition has a pH ranging from 5.0 to 10.5. 3.The dentifrice composition according to claim 1, wherein the dentifricecomposition comprises from 500 ppm to 5000 ppm of soluble zinc ion. 4.The dentifrice composition according to claim 1, wherein the dentifricecomposition further comprises another zinc ion source selected from thegroup consisting of zinc citrate, zinc gluconate, and combinationsthereof.
 5. The dentifrice composition according to claim 1, wherein thedentifrice composition is substantially free of stannous ion source. 6.The dentifrice composition according to claim 1, wherein the fluorideion is provided by a fluoride ion source selected from the groupconsisting of sodium fluoride, indium fluoride, amine fluoride, sodiummonofluorophosphate, potassium fluoride, zinc fluoride, and combinationsthereof.
 7. The dentifrice composition according to claim 1, wherein theglycine is present at a level of from about 0.5% to about 5%, by weightof the composition.
 8. The dentifrice composition according to claim 1,wherein the dentifrice composition further comprises from 0.01% to 5%,by weight of the composition, of a thickening system, wherein thethickening system is selected from a thickening polymer, a thickeningsilica, or a combination thereof.
 9. The dentifrice compositionaccording to claim 1, wherein zinc penetration within dental biofilm isgreater than 50%.
 10. The dentifrice composition according to claim 1,wherein the dentifrice composition further comprises from 1% to 35%, byweight of the composition, of an abrasive, wherein the abrasive isselected from a calcium-containing abrasive, a silica abrasive, or acombination thereof.
 11. The dentifrice composition according to claim1, wherein the dentifrice composition further comprises from 1% to 60%,by weight of the composition, of a humectant selected from sorbitol,glycerin, or a combination thereof.
 12. A method of treating dentalplaque biofilm in a subject, the method comprising the step of brushingthe subject's teeth with a dentifrice composition according to claim 1,wherein the brushing occurs at least once a day.